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Nephrotic Syndrome Children
Nephrotic Syndrome Children
Seminar
Search strategy
We searched the PubMed on-line database for all Englishlanguage papers on nephrotic syndrome published between
1996 and 2002. Our key search terms were nephrotic
syndrome, limited to all children. We chose papers relevant
to the paediatric population and pertaining to the topics of
epidemiology, pathophysiology, diagnosis, and management
as the basis of further review for this seminar.
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MCNS
Genetic disorders
Nephrotic-syndrome typical
Finnish-type congenital nephrotic syndrome
FSGS
Diffuse mesangial sclerosis
Denys-Drash syndrome
Schimke immuno-osseous dysplasia
Proteinuira with or without nephrotic syndrome
Nail-patella syndrome
Alports syndrome
Multisystem syndromes with or without nephrotic syndrome
Galloway-Mowat syndrome
Charcot-Marie-Tooth disease
Jeunes syndrome
Cockaynes syndrome
Laurence-Moon-Biedl-Bardet syndrome
FSGS
Secondary causes
Infections
Hepatitis B, C
HIV-1
Malaria
Syphilis
Toxoplasmosis
Drugs
Penicillamine
Gold
Non-steroidal anti-inflammatory drugs
Pamidronate
Interferon
Mercury
Heroin
Lithium
Immunological or allergic disorders
Castlemans disease
Kimuras disease
Bee sting
Food allergens
Associated with malignant disease
Lymphoma
Leukaemia
Glomerular hyperfiltration
Oligomeganephronia
Morbid obesity
Adaptation to nephron reduction
*May also be consequence of inflammatory glomerular disorders,
normally associated with features of nephritiseg, vasculitis,
lupus nephritis, membranoproliferative glomerulonephritis, IgA
nephropathy.
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Era 1
Era 2
Dates
Population
India (biopsies)4
USA (biopsies)5
North America,2
and Hong Kong3
(all cases)
Saudi Arabia
(all cases)6
n (%)
65 (20)
Dates
n (%)
157 (47)
36 (47)
148 (23)
46 (15)
Jan 1990
June 1992
Before 1990
196774
68 (23)
521 (7)
July 1992
Dec 1996
After 1990
198495
198392
132 (5)
19972001
3
5
2
1
6
4
7
Figure 2: Electron microscopic appearance of normal
glomerular epithelial cells in normal epithelial cells and
nephrotic syndrome, and mutations in podocyte proteins
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T cells
Circulating
permeability
factor
Permeability
inhibitory
factor
Proteinuria
Disease progression genes
(MCNS
FSGS?)
Angiotensin-converting enzyme
Genes dependent on ethnic origin
? immunosuppression responsiveness
? proteinuria susceptibility
? sclerosis susceptibility
Name
Location
Inheritance
Renal disease
19q13.1
1q25
19q13
11q2122
11p13
Recessive
Recessive
Dominant
Dominant
Dominant
Dominant
Recessive
Recessive
MCNS
LIM-homoeodomain protein
9q34
SW1/SNF2-related, matrix2q35
associated, actin-dependent regulator
of chromatin, subfamily a-like 1
Unknown
*Podocyte expression of SMARCAL1 presumptive but not yet established. Mutations in another protein, CD2-AP or NEPH1 (novel protein structurally related to nephrin)
cause congenital nephrotic syndrome in mice (reference 18). A mutational variant in the CD2AP gene has been identified in a few patients with steroid-resistant
nephrotic syndrome (reference 19).
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Diagnosis
Management
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Thromboembolic complications
Nephrotic patients are at significantly increased risk of
thrombosis, with complication rates reported as high as
40% in adults.120 Although thrombosis risk is apparently
lower in nephrotic children (1850%), these events can
be severe.121 Multiple factors contribute to the
dysregulated coagulation state of nephrotic syndrome
(figure 5). No one laboratory test can reliably predict the
real thrombotic risk. Fibrinogen concentration has been
proposed as a surrogate marker. Other factors that
increase thrombotic risk in nephrotic patients include
diuretic use, corticosteroid treatment, immobilisation,
and the presence of in-dwelling catheters. If a clot is noted
in a nephrotic child, investigation for an inherited
coagulation
abnormality
is
still
recommended.
Prophylactic anticoagulation is not recommended because
of its own inherent risks. However, after treatment of a
documented clot, use of prophylactic warfarin has been
recommended for at least 6 months, and perhaps during
future relapses.122 In-dwelling venous catheters should be
avoided, but if absolutely necessary, prophylactic
anticoagulation should be considered. Low-molecularweight heparin is an attractive alternative agent, but it
requires sufficient antithrombin III substrate to be
effective.122 Aspirin may also be considered for
anticoagulation, especially if thrombocytosis is severe.
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Cardiovascular disease
Multiple factors raise concerns for cardiovascular sequelae
in children with long-term nephrotic syndrome, including
exposure to corticosteroids, hyperlipidaemia, oxidant
stress, hypertension, hypercoagulability, and anaemia
(erythropoietin-responsive
anaemia
is
a
rare
complication123,124). Nephrotic syndrome in adulthood is
associated with an increased risk of coronary heart
disease.125 Myocardial infarction in young children with
nephrotic syndrome has been reported, but the relative
risk has not been calculated.126 In adults with nephrotic
syndrome, HMG-CoA-reductase inhibitors can control
hyperlipidaemia and limit its complications.127129 Whether
or not to treat hyperlipidaemia in nephrotic children has
been a source of controversy, especially since most
children have treatable renal disease.60 Adequate safety
and efficacy data for HMG-CoA-reductase inhibitors in
children are not available, despite small case series in
which decreased serum lipids have been reported.130,131
Persistent hyperlipidaemia in unremitting childhood
nephrotic syndrome is concerning, but there is little
evidence as yet to guide treatment or predict future
outcome.
References
Acknowledgments
1
2
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44 Sahali D, Pawlak A, Le Gouvello S, et al. Transcriptional and posttranscriptional alterations of I#B! in active minimal-change nephrotic
syndrome. J Am Soc Nephrol 2001; 12: 164858.
45 Winston JA, Bruggeman LA, Ross MD, et al. Nephropathy and
establishment of a renal reservoir of HIV type 1 during primary
infection. N Engl J Med 2001; 344: 197984.
46 Tanawattanacharoen S, Falk RJ, Jennette JC, Kopp JB. Parvovirus
B19 DNA in kidney tissue of patients with focal segmental
glomerulosclerosis. Am J Kidney Dis 2000; 35: 116674.
47 Li RM, Branton MH, Tanawattanacharoen S, Falk RA, Jennette JC,
Kopp JB. Molecular identification of SV40 infection in human
subjects and possible association with kidney disease.
J Am Soc Nephrol 2002; 13: 232030.
48 Stehman-Breen C, Alpers CE, Fleet WP, Johnson RJ. Focal
segmental glomerular sclerosis among patients infected with hepatitis
C virus. Nephron 1999; 81: 3740.
49 Humphreys MH. Mechanisms and management of nephrotic edema.
Kidney Int 1994; 45: 26681.
50 Vande Walle J, Donckerwolcke R, Boer P, van Isselt HW,
Koomans HA, Joles JA. Blood volume, colloid osmotic pressure and
F-cell ratio in children with the nephrotic syndrome. Kidney Int 1996;
49: 147177.
51 Geers AB, Koomans HA, Boer P, Dorhout Mees EJ. Plasma and
blood volumes in patients with the nephrotic syndrome. Nephron
1984; 38: 17073.
52 Dorhout Mees EJ, Geers AB, Koomans HA. Blood volume and
sodium retention in the nephrotic syndrome: a controversial
pathophysiological concept. Nephron 1984; 36: 20111.
53 Koomans HA, Geers AB, vd Meiracker AH, Roos JC, Boer P,
Dorhout Mees EJ. Effects of plasma volume expansion on renal salt
handling in patients with the nephrotic syndrome. Am J Nephrol
1984; 4: 22734.
54 Peterson C, Madsen B, Perlman A, Chan AY, Myers BD. Atrial
natriuretic peptide and the renal response to hypervolemia in
nephrotic humans. Kidney Int 1988; 34: 82531.
55 Palmer BF, Alpern RJ. Pathogenesis of edema formation in the
nephrotic syndrome. Kidney Int Suppl 1997; 59: S2127.
56 Ichikawa I, Rennke HG, Hoyer JR, et al. Role for intrarenal
mechanisms in the impaired salt excretion of experimental nephrotic
syndrome. J Clin Invest 1983; 71: 91103.
57 Usberti M, Gazzotti RM, Poiesi C, DAvanzo L, Ghielmi S.
Considerations on the sodium retention in nephrotic syndrome.
Am J Nephrol 1995; 15: 3847.
58 Schrier RW, Fassett RG. A critique of the overfill hypothesis of
sodium and water retention in the nephrotic syndrome. Kidney Int
1998; 53: 111117.
59 Vande Walle JG, Donckerwolcke RA. Pathogenesis of edema
formation in the nephrotic syndrome. Pediatr Nephrol 2001; 16:
28393.
60 Querfeld U. Should hyperlipidemia in children with the nephrotic
syndrome be treated? Pediatr Nephrol 1999; 13: 7784.
61 Vaziri ND, Liang K. Up-regulation of acyl-coenzyme A:cholesterol
acyltransferase (ACAT) in nephrotic syndrome. Kidney Int 2002; 61:
176975.
62 Shearer GC, Kaysen GA. Proteinuria and plasma compositional
changes contribute to defective lipoprotein catabolism in the
nephrotic syndrome by separate mechanisms. Am J Kidney Dis 2001;
37 (suppl 2): S11922.
63 Shearer GC, Stevenson FT, Atkinson DN, Jones H, Staprans I,
Kaysen GA. Hypoalbuminemia and proteinuria contribute separately
to reduced lipoprotein catabolism in the nephrotic syndrome.
Kidney Int 2001; 59: 17989.
64 Nakahara C, Kobayashi K, Hamaguchi H, Kanemoto K,
Kashiwagi R, Matsui A. Plasma lipoprotein (a) levels in children
with minimal lesion nephrotic syndrome. Pediatr Nephrol 1999; 13:
65761.
65 Webb NJ, Lewis MA, Iqbal J, Smart PJ, Lendon M,
Postlethwaite RJ. Childhood steroid-sensitive nephrotic
syndrome: does the histology matter? Am J Kidney Dis 1996;
27: 48488.
66 Gulati S, Sharma AP, Sharma RK, Gupta A, Gupta RK. Do current
recommendations for kidney biopsy in nephrotic syndrome need
modifications? Pediatr Nephrol 2002; 17: 40408.
67 Cattran DC. Idiopathic membranous glomerulonephritis. Kidney Int
2001; 59: 198394.
68 Ekka BK, Bagga A, Srivastava RN. Single- versus divided-dose
prednisolone therapy for relapses of nephrotic syndrome.
Pediatr Nephrol 1997; 11: 59799.
69 The primary nephrotic syndrome in children: identification of
patients with minimal change nephrotic syndrome from initial
response to prednisonea report of the International Study of
Kidney Disease in Children. J Pediatr 1981; 98: 56164.
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124
125
126
127
128
129
130
131
Clinical picture
Retinal detachment
Jennifer Ng, James Cleland, Peter Bergin
Department of Neurology, Auckland Hospital, Park Road, Private Bag 92024, Auckland, New Zealand (J Ng
Memorial Hospital, University of Rochester, Minnesota, USA (J Cleland MBChB)
MRCP,
P Bergin
FRACP);
Strong
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639